Somatosensory mechanical response and digit somatotopy within cortical areas of the postcentral gyrus in humans: An MEG study

Somatosensory evoked fields in response to compression (termed as Co) and decompression (termed as De) of glabrous skin (D1, thumb; D2, index finger; D5, little finger) were recorded. Although estimated equivalent current dipoles (ECDs) following stimulation of D1 and D5 were larger, but not significantly larger, in decompression than in compression, those of D2 were significantly larger (P = 0.035). The ECDs were located in the postcentral gyrus in the order of D5De, D2De, and D1De medially, posteriorly, and superiorly in decompression but not in compression (z‐value, F = 2.692, P = 0.031). The average distance of ECDs between D1 and D5 was longer in decompression (12.8 ± 1.6 mm) than in compression (9.1 ± 1.6 mm). Our data suggest that the cortical response for the commonly used digit D2 is functionally different from those for other digits (D1 and D5) that the somatotopic variability is greater in compression. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Micropapillary bladder cancer: Current treatment patterns and review of the literature

ObjectivesNo guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature.Materials and methodsA survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network–sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review.ResultsMost survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease.ConclusionsThe management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.     

Self-assembly of diclofenac prodrug into nanomicelles for enhancing the anti-inflammatory activity

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of various types of inflammatory conditions. Diclofenac is a very common NSAID that is utilized to relieve pain and reduce fever and, most importantly, inflammation. However, it suffers from low water solubility and a low dissolution profile. Therefore, we aim to develop a new drug delivery system based on the synthesis of amphiphilic structures that are capable of self assembling into nano-micelles which will be a water-soluble delivery system for the diclofenac. The amphiphilic structure consists of a hydrophilic moiety of triethylene glycol (TEG), polyethylene glycol PEG 400, or PEG 600 linked with the hydrophobic drug diclofenac through an ester linkage. The diclofenac derivatives were successfully synthesized as confirmed by nuclear magnetic resonance. Moreover, the formation of the micellar structure of the synthesized amphiphilic derivatives was confirmed by atomic force microscopy obtaining a spherical shape of the micelles with average diameters of 200 nm for Dic-PEG400-Dic, and 110 nm for Dic-PEG600-Dic. The critical micelle concentration has been determined as 2.7 × 10⁻³ mg mL⁻¹ for Dic-PEG400-Dic, and 1 × 10⁻⁴ mg mL⁻¹ for Dic-PEG600-Dic. The in vitro diclofenac release profile by esterase enzyme was conducted and showed almost complete conversion to free diclofenac within 35 h in the case of Dic-PEG400-Dic micelles and more than 85% of Dic-PEG600-Dic micelles. Then the anti-inflammatory activity was determined by testing the TNF-α production in LPS-stimulated Balb/c mice. Diclofenac micelles significantly suppressed TNF-α production after a 5 mg kg⁻¹ dose was given. The developed micelles showed TNF-α inhibition up to 87.4% and 84% after 48 hours of treatment in the case of Dic-PEG400-Dic and Dic-PEG600-Dic micelles respectively in comparison to 42.3% in the case of diclofenac alone. Dic-PEG400-Dic micelles showed the most potent anti-inflammatory activity with improved TNF-α suppression through time progress. Therefore, the developed nano-micelles provide a facile synthetic approach to enhance diclofenac water solubility, improve the anti-inflammatory effect and achieve a sustained release profile to get better patient compliance.

Amphiphilic diclofenac prodrugs were successfully synthesized and self-assembled into the nano-micellar structures that have improved the anti-inflammatory activity in vivo.     

Recent advances in the diagnosis and treatment of deep vein thrombosis: a regional consensus

Considerable progress has been made in the understanding of the risk factors for venous thromboembolism (VTE). The clinical applications of molecular techniques have allowed identification of important inherited, yet not uncommon, risk factors for VTE, such as mutations that cause Factor V Leiden and prothrombin G20210A. However, advances in our understanding have raised several questions regarding the need for, and duration of anticoagulation. At the end of the treatment period, low molecular weight heparins have become the drugs of choice and standard-of-care for VTE. In this review, cost effective diagnostic approaches for patients with suspected deep vein thrombosis, and recommended treatment options using evidence-based approaches, are described.     

The day we need to remember

The crime of 11 September 2002 is another aspect of the military culture of the last 5,000 years, which is also reflected in the continued conflict in Israel and Palestine. No real attempt has been made to convert the Oslo agreement into a permanent peace settlement, which must include a viable Palestinian state. Nevertheless, all acts of terror must be condemned whatever their motivation. The support of the United States is essential for a Palestinian state to come into being.     

Laminar Necrosis of Placental Membranes: A Histologic Sign of Uteroplacental Hypoxia

Laminar necrosis of placental membranes (LN), a band of coagulative necrosis at the choriodecidual interphase, is a histologic lesion of unclear pathogenesis that has been reported in placentas from preeclampsia, preterm premature rupture of membranes, and preterm abruption. To better explore other possible correlations of LN, we performed a retrospective case-control study in which data on pregnancy risks and outcomes, neonate conditions, and placental gross, routine microscopic, and selected immunohistochemistry examinations in 52 consecutive cases of LN were compared with 52 gestational age-matched control cases without LN. Maternal hypertensive disorders and combinations of 2 or more maternal, fetal, neonatal, or placental conditions known to be potentially associated with uteroplacental hypoxia were more prevalent in patients with LN than in control patients. By immunohistochemistry, LN areas were positive for complement 9 (marker of necrosis) and negative for active caspase 3 (marker of irreversible apoptosis), nitrotyrosine residues (marker of oxidative stress), and Ki-67 (proliferation marker), thus confirming their necrotic rather than apoptotic nature. However, LN areas were flanked by caspase 3 positivity, and the positivity for nitrotyrosine residues was more pronounced in the decidua and mesenchyme in the same membrane rolls as LN, which indicates a probable role of apoptosis and oxidative stress in the development of LN. Based on these immunohistochemical results and clinicopathologic correlations, we believe LN should be recognized and reported as a hypoxic placental lesion.Presented at the 9th Meeting of the International Federation of Placenta Associations; Mainz, Germany; September 24 to 27, 2003